Definition/Key Clinical Features

• Malignancy arising from a melanocyte; vast majority occur in skin
• Possible melanoma with any pigmented skin lesion meeting following criteria:
  • Recent change
  • Asymmetry
  • Border irregularity
  • Color variation
  • Diameter > 6 mm
  • Changes color, shape, size relative to patient's other moles
• Moles (nevi) are strongest phenotypic melanoma risk markers, especially increased numbers of moles and atypical moles (dysplastic nevi) (i.e., those that are large [> 5 mm] with variegate pigmentation, ill-defined borders)

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Differential Diagnosis

• Dysplastic nevus
• Lentigines
• Sunburn freckles
• Traumatized nevus
• Thrombosed angioma
• Pigmented basal cell carcinoma
• Pigmented Bowen disease
• Dermatofibroma
• Atypical seborrheic keratosis
• Amelanotic melanoma
• Spitz nevus

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Best Tests

• Simple visual inspection, including scalp, genitalia, soles of feet
• Risk factors
• Patient history of changed lesion
• Nevi (large number, atypical)
• Fair complexion
• Tendency to burn
• Inability to tan
• Freckling
• Family history of melanoma
• Screening family members for melanoma (particularly multiple melanoma) may be useful
• Diagnostic aids
• Dermoscopy
• Baseline photographs of entire body
• Definitive diagnosis: biopsy by full-thickness excision preferred

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Best Therapy

Primary Site

• Primary cutaneous melanoma managed surgically with definitive reexcision
  • 1-cm margins for melanomas < 1 mm thick
  • 2-cm margins for melanomas 1–4 mm thick
  • 2- to 4-cm margin for melanomas > 4 mm thick
  • Primary closure and reconstructive flaps preferable to skin grafts

Lymph Nodes

• Therapeutic lymph node dissection for clinically evident regional lymph node disease
• Sentinel lymph node biopsy increasingly used for melanoma > 1 mm thick; sentinel node status strongly correlated with 5-yr survival

Adjuvant Therapy

• For patients with cutaneous or regional disease who are surgically rendered free of disease but at high risk for recurrence or metastasis
• High-dose regimen of interferon alfa approved by FDA
• Clinical trials of adjuvant vaccines to be considered

In-Transit Metastases

• Slow-growing individual occurrences managed surgically
• Limb perfusion therapy for extensive occurrences confined to extremity

Distant Metastases

• Monotherapy with dacarbazine is the standard treatment against which all others are judged
• Interleukin-2 is FDA-approved
• Clinical trials of multidrug treatment and immunologic therapies to be considered

Chemotherapeutic agents

• Dacarbazine: for distant metastatic disease; objective responses in approximately 5%–20%; durable complete responses rare
• Interferon alfa: in adjuvant setting; two studies showed small but statistically significant improvement in overall survival
• Dose: 20 million U/m² I.V. daily for 1 mo followed by 10 million U/m² S.C. three times/wk x 48 wk
• Interleukin-2: low response rate but some responses durable
• Dose: 600,000–720,000 U/kg S.C. t.i.d. on days 1–5, 15–19

Best Quality

• Screening for additional primary melanomas on follow-up
  • In dysplastic nevi, melanoma detection predicated on specialized visual exam aided by self-exam and professional follow-up to identify changing lesion
  • Photographically assisted follow-up in high-risk individuals

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Best References

Tsao H, et al: N Engl J Med 351:998, 2004 [PMID 15342808]

September 2006